José María Aguado

Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study.

Background. The efficacy of the combination of voriconazole and caspofungin when used as primary therapy for invasive aspergillosis in organ transplant recipients has not been defined. Methods. Transplant recipients who received voriconazole and caspofungin (n=40) as primary therapy for invasive aspergillosis (proven or probable) in a prospective multicenter study between 2003 and 2005 were compared to a control group comprising a cohort of consecutive transplant recipients between 1999 and 2002 who had received a lipid formulation of AmB as primary therapy (n=47). In vitro antifungal testing of Aspergillus isolates to combination therapy was correlated with clinical outcome. Results. Survival at 90 days was 67.5% (27/40) in the cases, and 51% (24/47) in the control group (HR 0.58, 95% CI, 0.30–1.14, P=0.117). However, in transplant recipients with renal failure (adjusted HR 0.32, 95% CI: 0.12–0.85, P=0.022), and in those with A. fumigatus infection (adjusted HR 0.37, 95% CI: 0.16–0.84, P=0.019), combination therapy was independently associated with an improved 90-day survival in multivariate analysis. No correlation was found between in vitro antifungal interactions of the Aspergillus isolates to the combination of voriconazole and caspofungin and clinical outcome. Conclusions. Combination of voriconazole and caspofungin might be considered preferable therapy for subsets of organ transplant recipients with invasive aspergillosis, such as those with renal failure or A. fumigatus infection.

Clinical Presentation And Outcome Of Tuberculosis In Kidney, Liver, And Heart Transplant Recipients In Spain1

BACKGROUND Tuberculosis is unusual in transplant recipients. The incidence, clinical manifestations, and optimal treatment of this disease in this population has not been adequately defined. The present study was undertaken to assess the incidence, clinical features, and response to therapy of Mycobacterium tuberculosis infection in solid-organ transplant recipients. METHODS We evaluated retrospectively the incidence, clinical characteristics, diagnostic procedures, antituberculous treatment, clinical course, and factors influencing mortality in 51 solid-organ transplant recipients who developed tuberculosis after transplantation. We also reviewed the world literature on tuberculosis in solid-organ transplantation. RESULTS The overall incidence of tuberculosis was 0.8%. The localization was pulmonary in 63% of the cases, disseminated in 25%, and extrapulmonary in 12%. Tuberculosis developed from 15 days to 13 years after surgery (mean, 23 months). In one third of the cases, diagnosis was not suspected initially, and in three cases, diagnosis was made at necropsy. Fever was the most frequent symptom, followed by constitutional symptoms, cough, respiratory insufficiency, and pleuritic pain. Fifteen patients (33%) developed hepatotoxicity during treatment; hepatotoxicity was severe in seven cases. Hepatotoxicity was higher in patients receiving four or more antituberculous drugs (50%) than in patients receiving three drugs (21%; P=0.03). Serum levels of cyclosporine decreased in the 26 patients under the simultaneous use of rifampin. Nine of them (35%) developed acute rejection, and five (56%) died, in comparison with 3 of 17 patients (18%) who did not develop rejection after the use of cyclosporine and rifampin (P=0.03). Although microbiological response was favorable in 94% of the 35 patients who completed 6 or more months of treatment, 16 other patients (31%) died before diagnosis or in the course of treatment. None of the patients treated for more than 9 months died as a consequence of tuberculosis, whereas the mortality rate was 33% among those treated for 6 to 9 months (P=0.03). Use of antilymphocyte antibodies or high doses of steroids for acute rejection before tuberculosis was associated with a higher mortality rate. CONCLUSIONS M tuberculosis causes serious and potentially life-threatening disease in solid-organ transplant recipients. Treatment with at least three drugs during 9 months or more, avoiding the use of rifampin, appears to be appropriate.

FASCIOLIASIS IN DEVELOPED COUNTRIES : A REVIEW OF CLASSIC AND ABERRANT FORMS OF THE DISEASE

Cases of human infestation by Fasciola hepatica are not uncommon in Spain and other European countries. We report our experience with 20 patients diagnosed from 1982 to 1991 and present a critical review of published cases from western countries. Because F. hepatica has a special tropism for the liver, abdominal pain, hepatomegaly, and constitutional symptoms are among the most common manifestations of acute-stage fascioliasis. However, in the chronic stage, biliary colic and cholangitis are the predominant manifestations. The clinical spectrum of fascioliasis is variable, and patients may present with extrahepatic abnormalities, such as pulmonary infiltrates, pleuropericarditis, meningitis, or lymphadenopathy. Therefore, a high index of suspicion is required to establish a correct diagnosis. Eosinophilia is the most frequent laboratory abnormality. The CT scan has become a useful technique in the diagnostic work-up. A definitive diagnosis may be established by the observation of parasite ova in the feces, but most cases may be diagnosed by serologic methods. Triclabendazole and bithionol are the most effective drugs against F. hepatica. The efficacy of praziquantel is controversial.

Tuberculosis in solid-organ transplant recipients: consensus statement of the group for the study of infection in transplant recipients (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology.

Tuberculosis is a particularly important condition in solid-organ transplant recipients because of the delay in treatment caused by the difficulties involved in its diagnosis and because of the pharmacological toxicity associated with this treatment. Both treatment delay and toxicity are responsible for the many clinical complications of and high mortality associated with tuberculosis in this population. The Consensus Statement from the Spanish Group for the Study of Infectious Diseases in Transplant Recipients defines the indications for treatment of latent tuberculosis infection in solid-organ transplant recipients, especially in patients with a high risk of pharmacological toxicity, as is the case with liver recipients. We established a series of recommendations regarding the types of drugs and the duration of treatment of tuberculosis in solid-organ recipients, giving special attention to pharmacological interactions between rifampin and immunosuppressive drugs (cyclosporine, tacrolimus, rapamycin, and corticosteroids).

Zygomycosis in Solid Organ Transplant Recipients: A Prospective, Matched Case-Control Study to Assess Risks for Disease and Outcome

BACKGROUND Clinical characteristics, risks, and outcomes in solid organ transplant (SOT) recipients with zygomycosis in the era of modern immunosuppressive and newer antifungal agent use have not been defined. METHODS In a matched case-controlled study, SOT recipients with zygomycosis were prospectively studied. The primary outcome measure was success (complete or partial response) at 90 days. RESULTS Renal failure (odds ratio [OR], 3.17; P = .010), diabetes mellitus (OR, 8.11; P < .001), and prior voriconazole and/or caspofungin use (OR, 4.41; P = .033) were associated with a higher risk of zygomycosis, whereas tacrolimus (OR, 0.23; P = .002) was associated with a lower risk of zygomycosis. Liver transplant recipients were more likely to have disseminated disease (OR, 5.48; P = .021) and developed zygomycosis earlier after transplantation than did other SOT recipients (median, 0.8 vs 5.7 months; P < .001). Overall the treatment success rate was 60%. Renal failure (OR, 11.3; P = .023) and disseminated disease (OR, 14.6; P = .027) were independently predictive of treatment failure, whereas surgical resection was associated with treatment success (OR, 33.3; P = .003). The success rate with liposomal amphotericin B was 4-fold higher even when controlling for the aforementioned variables. CONCLUSIONS The risks identified for zygomycosis and for disseminated disease, including those that were previously unrecognized, have implications for further elucidating the biologic basis and for optimizing outcomes in SOT recipients with zygomycosis.

Tuberculosis after Solid-Organ Transplant: Incidence, Risk Factors, and Clinical Characteristics in the RESITRA (Spanish Network of Infection in Transplantation) Cohort

BACKGROUND It is necessary to clarify the incidence of and risk factors for tuberculosis (TB) among solid-organ transplant (SOT) recipients as well as changes in the chronology, clinical presentation, and prognosis of the disease. METHODS A total of 4388 SOT recipients were monitored prospectively at 16 transplant centers included in the Spanish Network for Research in Infectious Diseases (REIPI). TB episodes were studied, and the incidence rate was calculated. Certain variables were analyzed, by Cox regression analysis, as potential risk factors for TB. RESULTS Among the 4388 SOT recipients, 21 cases of TB were reported (0.48%). The median duration of follow-up was 360 days (range, 0-720 days). The global incidence of TB was 512 cases per 10(5) patients per year (95% confidence interval [CI], 317-783), which was higher than that in the general population in Spain (18.9 cases per 10(5) inhabitants per year; relative risk [RR], 26.6). The highest incidence (2072 cases per 10(5) patients per year; 95% CI, 565-5306) was observed among lung transplant recipients (RR, 73.3). Of the TB cases, 95% occurred within the first year after transplant, and 76% were pulmonary forms. Crude mortality was 19.0%, and attributable mortality was 9.5%. Multivariate analysis identified recipient age (RR, 1.05; 95% CI, 1.0-1.1) and receipt of a lung transplant (RR, 5.6; 95%, 1.9-16.9) as independent risk factors. CONCLUSIONS TB incidence is increased among SOT recipients. The risk factors identified were age and receipt of a lung transplant. TB-attributable mortality (9.5%) is still high.

Seasonal and Pandemic A (H1N1) 2009 influenza vaccination coverage and attitudes among health-care workers in a Spanish University Hospital

Abstract Influenza vaccination coverage among health-care workers (HCWs) remains the lowest compared with other priority groups for immunization. Little is known about the acceptability and compliance with the pandemic (H1N1) 2009 influenza vaccine among HCWs during the current campaign. Between 23 December 2009 and 13 January 2010, once the workplace vaccination program was over, we conducted a cross-sectional, questionnaire-based survey at the University Hospital 12 de Octubre (Madrid, Spain). Five hundred twenty-seven HCWs were asked about their influenza immunization history during the 2009–2010 season, as well as the reasons for accepting or declining either the seasonal or pandemic vaccines. Multiple logistic-regression analysis was preformed to identify variables associated with immunization acceptance. A total of 262 HCWs (49.7%) reported having received the seasonal vaccine, while only 87 (16.5%) affirmed having received the pandemic influenza (H1N1) 2009 vaccine. “Self-protection” and “protection of the patient” were the most frequently adduced reasons for acceptance of the pandemic vaccination, whereas the existence of “doubts about vaccine efficacy” and “fear of adverse reactions” were the main arguments for refusal. Simultaneous receipt of the seasonal vaccine (odds ratio [OR]: 0.27; 95% confidence interval [95% CI]: 0.14–0.52) and being a staff (OR: 0.08; 95% CI: 0.04–0.19) or a resident physician (OR: 0.16; 95% CI: 0.05–0.50) emerged as independent predictors for pandemic vaccine acceptance, whereas self-reported membership of a priority group was associated with refusal (OR: 5.98; 95% CI: 1.35–26.5). The pandemic (H1N1) 2009 influenza vaccination coverage among the HCWs in our institution was very low (16.5%), suggesting the role of specific attitudinal barriers and misconceptions about immunization in a global pandemic scenario.

Impact of Current Transplantation Management on the Development of Cytomegalovirus Disease after Renal Transplantation

BACKGROUND Current advances in transplantation practices may influence the development of cytomegalovirus (CMV) disease after renal transplantation. METHODS From September 2003 through February 2005, 1470 renal transplant recipients (55 of whom were kidney-pancreas transplant recipients) were prospectively studied in the 16 transplant centers affiliated with the Spanish Network of Infection in Transplantation, with use of an ad hoc-designed online database. Univariate and multivariate analyses with logistic regression were performed to detect risk factors for CMV disease. RESULTS A total of 105 episodes of CMV disease (37 with visceral involvement) developed in 99 (6.7%) of 1470 patients. Attributable mortality appeared in 1 (1.0%) of 105 cases. Multivariate analysis showed that, apart from CMV serological mismatch, presence of rejection episodes, and the use of antilymphocitic drugs, a simultaneous pancreas transplantation (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.5-9), use of cyclosporine (OR, 1.7; 95% CI, 1.18-2.9), a donor >60 years of age (OR, 2.3; 95% CI, 1.5-3.7), and chronic graft malfunction (OR, 1.8; 95% CI, 1.14-2.9) were independently associated with CMV disease, whereas use of sirolimus had a protective effect (OR, 0.27; 95% CI, 0.1-0.78). CONCLUSIONS Additional risk factors related to current transplantation practices influence the epidemiology of CMV after renal transplantation and should be taken into account in the design of prophylactic strategies in this population of kidney or kidney-pancreas recipients.

Clinical Significance of Donor-Unrecognized Bacteremia in the Outcome of Solid-Organ Transplant Recipients

We evaluated the clinical significance of unrecognized bacteremia in the organ donor (i.e., blood culture results that were reported to be positive after transplantation) on the outcome of transplant recipients. Twenty-nine of 569 liver and heart donors (5%) had bacteremia at the time of organ procurement, but there were no documented instances of transmission of the isolated bacteria from the donor to the recipient. Unrecognized bacteremia in the donor does not have a negative clinical impact on the outcome of organ transplant recipients.

Bacterial urinary tract infection after solid organ transplantation in the RESITRA cohort.

Urinary tract infection (UTI) is the most common infection in renal transplant patients, but it is necessary to determine the risk factors for bacterial UTI in recipients of other solid organ transplants (SOTs), as well as changes in etiology, clinical presentation, and prognosis.